αEβ7 (CD103) Expression Identifies a Highly Active, Tonsil-Resident Effector-Memory CTL Population

Abstract

The characterization of antiviral CTL responses has largely been limited to assessing Ag-specific immune responses in the peripheral blood. Consequently, there is an incomplete understanding of the cellular immune responses at mucosal sites where many viruses enter and initially replicate and how the Ag specificity and activation status of CTL derived from these mucosal sites may differ from that of blood-derived CTL. In this study, we show that EBV-specific CTL responses in the tonsils are of comparable specificity and breadth but of a significantly higher magnitude compared with responses in the peripheral blood. EBV-specific, tonsil-resident, but not PBMC-derived, T cells expressed the integrin/activation marker CD103 (αEβ7), consistent with the detection of its ligand, E-cadherin, on tonsillar squamous cells. These CD8-positive, CD103-positive, tonsil-derived CTL were largely CCR7- and CD45RA- negative effector-memory cells and responded to lower Ag concentrations in in vitro assays than their CD103-negative PBMC-derived counterparts. Thus, EBV-specific CTL in the tonsil, a crucial site for EBV entry and replication, are of greater magnitude and phenotypically distinct from CTL in the peripheral blood and may be important for effective control of this orally transmitted virus.

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

“…Respiratory tract CD8 + T cells, but not peripheral blood counterparts with the same antigenic specificity, are highly positive for CD103 and have the effector memory phenotype (43). In human BAL, a much greater fraction of CD8 + and CD4 + T cells expresses CD103, as compared with that in the peripheral blood (31).…”

CD8+CD103+ Tumor–Infiltrating Lymphocytes Are Tumor-Specific Tissue-Resident Memory T Cells and a Prognostic Factor for Survival in Lung Cancer Patients

“…Thus, TGF-b1, considered as an immunosuppressive cytokine, can control immune responses to viral infections and tumors via induction of CD103 and formation of CD8 + CD103 + T RM T cells. The CD103 2 lymphocytes observed in several NSCLC tumors might represent either nonspecific T cells passing through the lung tumor lesion or recently recruited tumor- which CD103 is expressed on CD8 + T cells specific to influenza virus in the lung (24), EBV in the tonsil (32), and cancer testis Ag NY-ESO-1 in ovarian cancer (9). In the latter and present studies, CD103 + T cells expressed high levels of PD-1, which has been defined as a biomarker of tumor-specific T cells (33).…”

Systemic and Mucosal Infection Program Protective Memory CD8 T Cells in the Vaginal Mucosa

“…Lymphocytes in mucosal environments have been shown to express several specific adhesion molecules (21). CD103 is an integrin and activation marker that has been shown to bind E-cadherin, an integrin receptor shown to have high expression on intestinal endothelial cells and tonsil (21,22).…”

“…CD103 is an integrin and activation marker that has been shown to bind E-cadherin, an integrin receptor shown to have high expression on intestinal endothelial cells and tonsil (21,22). CD103 expression has been shown to be high on Ag-specific memory intestinal intraepithelial lymphocytes (IELs) and EBV-specific tonsil resident effectormemory CTLs (21,23). We determined CD103 expression on Agspecific CD8 T cells in the spleen, PBMC, ILN, IEL, and vaginal tract on day 8 and day 400 of memory ( Fig.…”